The ultimate goal of our research program is the development, understanding, and proper clinical use of surface attached immunological adjuvants prepared from purified-synthetic microbial components and used alone or combined with tumor antigen for both the therapeutic and prophylactic treatment of cancer. Based on initial work with BCG, we have, during the past two years of this grant, investigated and shown that intravenous "second generation" microbial adjuvants composed of trehalose dimycolate and cell wall skeleton are well tolerated and effective. This request is for basic and clinical studies for the development of a stable, totally defined third generation adjuvant to be used alone and combined with antigen as a vaccine. Trials, both locally and on a group level, are anticipated. The specific aims for the project period are: (1) to develop a stable, chemically defined, optimally active adjuvant; (2) to do appropriate clinical trials of oil attached microbial components and lipid A; (3) to initiate clinical trials of "third" generation adjuvants; (4) based on the animal studies and (5) to initiate Phase I-II trials of active specific immunotherapy. The methodology will be to use standard models and techniques to develop the adjuvant, isolate tumor antigen, and to thoroughly investigate active specific immunotherapy in the models. The data will be used to design subsequent clinical studies. Components of the adjuvant will be replaced with muramyl depeptide or its derivatives. Non-toxic lipid A will be investigated as a major component of the adjuvant. Concurrently immune testing will be done to define the alteration which occur with therapy and the relationship of initial immune status with response. The studies will lead to initial clinical studies of antigen combined with adjuvant for treatment and prophylaxis in patients with cancer.